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Yeast Applications in Gene Mutation
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Yeast Applications in Gene Mutation

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (1 July 2021) | Viewed by 15675

Special Issue Editor

Dr. Alvaro Galli

E-Mail Website
Guest Editor
Yeast Genetics and Genomics Group, Laboratory of Functional Genetics and Genomics, Institute of Clinical Physiology CNR, Via Moruzzi 1, 56125 Pisa, Italy
Interests: homologous recombination; yeast functional assays; genome wide screening; cancer genetics; BRCA1 variant classification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Yeast is an excellent model to investigate the molecular mechanisms and genetic control of mutations and, in general, chromosomal instability. Over the years, yeast has given a valuable contribution to our understanding biological relations between mutagenesis and cancer. Moreover, yeast-based functional assays have been developed to characterize cancer-associated mutations in several tumor-suppressor genes; “humanized” yeast strains have been constructed and validated in order to investigate the genetic control of fundamental biological processes and their association to human diseases. Therefore, yeast represents a very helpful tool to investigate DNA repair and mutagenesis pathways that are involved in gene mutation. Recently, as cutting-edge research, several high-throughput yeast screenings have been reported where up to several thousands of mutations have been generated and analyzed simultaneously. This Special Issue will present recent advances on genetic approaches in yeast to study and characterize gene mutations involved in biological processes and diseases. Research articles and reviews will be considered for publication in this Issue.

Dr. Alvaro Galli
Guest Editor

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Keywords

  • DNA repair and disease
  • Yeast-based mutation assays
  • Genome instability
  • Yeast functional assays
  • High-throughput screening

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Published Papers (4 papers)

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Research

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12 pages, 15980 KiB  
Article
Role of Calcium/Calcineurin Signalling in Regulating Intracellular Reactive Oxygen Species Homeostasis in Saccharomyces cerevisiae
by Guohui Li, Wenxuan Fu, Yu Deng and Yunying Zhao
Genes 2021, 12(9), 1311; https://doi.org/10.3390/genes12091311 - 25 Aug 2021
Cited by 5 | Viewed by 2880
Abstract
The calcium/calcineurin signalling pathway is required for cell survival under various environmental stresses. Using Saccharomyces cerevisiae, we explored the mechanism underlying calcium-regulated homeostasis of intracellular reactive oxygen species (ROS). We found that deletion of acyltransferase Akr1 and C-5 sterol desaturase Erg3 increased [...] Read more.
The calcium/calcineurin signalling pathway is required for cell survival under various environmental stresses. Using Saccharomyces cerevisiae, we explored the mechanism underlying calcium-regulated homeostasis of intracellular reactive oxygen species (ROS). We found that deletion of acyltransferase Akr1 and C-5 sterol desaturase Erg3 increased the intracellular ROS levels and cell death, and this could be inhibited by the addition of calcium. The hexose transporter Hxt1 and the amino acid permease Agp1 play crucial roles in maintaining intracellular ROS levels, and calcium induced the expression of the HXT1 and AGP1 genes. The cytosolic calcium concentration was decreased in both the akr1Δ and erg3Δ mutants relative to wild-type cells, potentially lowering basal expression of HXT1 and AGP1. Moreover, the calcium/calcineurin signalling pathway also induced the expression of AKR1 and ERG3, indicating that Akr1 and Erg3 might perform functions that help yeast cells to survive under high calcium concentrations. Our results provided mechanistic insight into how calcium regulated intracellular ROS levels in yeast. Full article
(This article belongs to the Special Issue Yeast Applications in Gene Mutation)
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12 pages, 978 KiB  
Article
Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay
by Paola Monti, Vaclav Brazda, Natália Bohálová, Otília Porubiaková, Paola Menichini, Andrea Speciale, Renata Bocciardi, Alberto Inga and Gilberto Fronza
Genes 2021, 12(2), 277; https://doi.org/10.3390/genes12020277 - 15 Feb 2021
Cited by 5 | Viewed by 2949
Abstract
P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further [...] Read more.
P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribute to the generation of multiple isoforms. P53 family proteins can influence a plethora of cellular pathways mainly through the direct binding to specific DNA sequences known as response elements (REs), and the transactivation of the corresponding target genes. However, the transcriptional activation by P53 family members can be regulated at multiple levels, including the DNA topology at responsive promoters. Here, by using a yeast-based functional assay, we evaluated the influence that a G-quadruplex (G4) prone sequence adjacent to the p53 RE derived from the apoptotic PUMA target gene can exert on the transactivation potential of full-length and N-terminal truncated P53 family α isoforms (wild-type and mutant). Our results show that the presence of a G4 prone sequence upstream or downstream of the P53 RE leads to significant changes in the relative activity of P53 family proteins, emphasizing the potential role of structural DNA features as modifiers of P53 family functions at target promoter sites. Full article
(This article belongs to the Special Issue Yeast Applications in Gene Mutation)
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Review

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17 pages, 1484 KiB  
Review
Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants
by Tiziana Cervelli and Alvaro Galli
Genes 2021, 12(9), 1303; https://doi.org/10.3390/genes12091303 - 24 Aug 2021
Cited by 13 | Viewed by 5335
Abstract
At present, the great challenge in human genetics is to provide significance to the growing amount of human disease-associated gene variants identified by next generation DNA sequencing technologies. Increasing evidences suggest that model organisms are of pivotal importance to addressing this issue. Due [...] Read more.
At present, the great challenge in human genetics is to provide significance to the growing amount of human disease-associated gene variants identified by next generation DNA sequencing technologies. Increasing evidences suggest that model organisms are of pivotal importance to addressing this issue. Due to its genetic tractability, the yeast Saccharomyces cerevisiae represents a valuable model organism for understanding human genetic variability. In the present review, we show how S. cerevisiae has been used to study variants of genes involved in different diseases and in different pathways, highlighting the versatility of this model organism. Full article
(This article belongs to the Special Issue Yeast Applications in Gene Mutation)
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28 pages, 1151 KiB  
Review
The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases
by Camilla Ceccatelli Berti, Giulia di Punzio, Cristina Dallabona, Enrico Baruffini, Paola Goffrini, Tiziana Lodi and Claudia Donnini
Genes 2021, 12(2), 300; https://doi.org/10.3390/genes12020300 - 20 Feb 2021
Cited by 21 | Viewed by 3632
Abstract
The increasing application of next generation sequencing approaches to the analysis of human exome and whole genome data has enabled the identification of novel variants and new genes involved in mitochondrial diseases. The ability of surviving in the absence of oxidative phosphorylation (OXPHOS) [...] Read more.
The increasing application of next generation sequencing approaches to the analysis of human exome and whole genome data has enabled the identification of novel variants and new genes involved in mitochondrial diseases. The ability of surviving in the absence of oxidative phosphorylation (OXPHOS) and mitochondrial genome makes the yeast Saccharomyces cerevisiae an excellent model system for investigating the role of these new variants in mitochondrial-related conditions and dissecting the molecular mechanisms associated with these diseases. The aim of this review was to highlight the main advantages offered by this model for the study of mitochondrial diseases, from the validation and characterisation of novel mutations to the dissection of the role played by genes in mitochondrial functionality and the discovery of potential therapeutic molecules. The review also provides a summary of the main contributions to the understanding of mitochondrial diseases emerged from the study of this simple eukaryotic organism. Full article
(This article belongs to the Special Issue Yeast Applications in Gene Mutation)
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